Risk of cardiovascular and cerebrovascular events and mortality in patients with migraine receiving prophylactic treatments: An observational cohort study

Introduction This study quantified risks of cardiovascular, cerebrovascular, and mortality events among patients with migraine receiving prophylaxis. Methods Patients with migraine aged 18–65 years were identified from 2010 through 2015 within a United States administrative claims database. Topiramate initiators during follow-up were propensity score-matched separately to anticonvulsant, cardiovascular treatment, antidepressant, and other prophylactic treatment initiators. Incident outcomes were identified, and hazard ratios were calculated comparing outcome occurrence among topiramate initiators relative to each comparator. A case-control analysis was nested within the full migraine cohort, and odds ratios quantified the association between outcomes and use or non-use of individual prophylactic treatments (anticonvulsants, serotonin norepinephrine reuptake inhibitors, beta blockers, antihypertensives, tricyclic antidepressants, and other prophylactic treatments). Results The cohort included 119,243 patients with migraine. The matched topiramate initiators had a lower mortality risk versus antidepressant (hazard ratio: 0.44, 95% CI: 0.24, 0.83) and anticonvulsant initiators (hazard ratio: 0.45, 95% CI: 0.25, 0.84). In the case-control analysis, increased risks of several outcomes were observed with all prophylactic treatments relative to non-use of that treatment (odds ratios range from 1.54 to 7.90, and 95% CIs exclude 1.0) except for topiramate and calcium channel blockers. Conclusions Although increased risks for several outcomes were observed with certain prophylactic treatments, the treatments other than topiramate likely represent markers for outcome risk factors that developed or progressed after cohort entry, rather than being a direct effect of the treatments. Factors including migraine severity, frequency, and other treatment indications should be considered in future migraine prophylactic treatment safety assessments.